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The Art, Science, and Gut-Wrenching Story of Antibiotics

Fall is upon us as the leaves change colors, temperatures are cooler, and density altitudes provide better performances for our flights. Influenza (flu), sinusitis, and pneumonia will soon knock on our door.

The opportunity to be a pharmacist has also given me an insight into Mother Nature. Our vegetable garden is at the end of its productive life cycle. As I work in the soil, I observe the sustenance and nutrients given to the tomatoes and cucumbers in our garden. I also see the soil as the source of antibiotics I have utilized to treat bacterial infections. 

The history of antibiotics goes back millennia. Poultices (soft, moist masses) made of moldy bread were used to treat open wounds in Serbia, China, Greece, and Egypt more than 2,000 years ago. Ebers papyrus from 1550 BC is the oldest preserved medical document and includes moldy bread and medicinal soil amongst its list of remedies (Journal of Neurology, Neurosurgery & Psychiatry, 1999). About one-third of antibiotics since the 1920s have originated from a bacteria group called actinomycetes. Actinomycetes are predominately found in soil and give the soil an earthy smell in the topsoil. The unique characteristic of actinomycetes is that oxygen is not needed for them to grow.

Five other antibiotics come from bacteria such as Bacillus and Pseudomonas. Pseudomonas aeruginosa is a highly virulent bacteria seen in drug-resistant infections in the lungs of cancer patients. Five antibiotics come from fungi. Penicillin is included in this group, as it comes from a fungus called Penicillium. Scottish researcher Alexander Fleming discovered penicillin by accident in 1928. He noticed that a mold was growing on a staphylococcus bacteria culture plate in his lab and that the bacteria around the mold did not grow. Amazingly, it took over 20 years before penicillin was introduced clinically in 1949. Today, sixty percent of antibiotics are synthetically manufactured and not derived from organic sources. According to the Centers for Disease Control and Prevention (CDC), healthcare providers prescribed 236.4 million antibiotic prescriptions in 2022. That is close to seven out of ten patients that are prescribed antibiotics. Physician assistants and nurse practitioners prescribed the most antibiotics (84.4 million), followed by primary care physicians (70 million) and dentists (25 million). Approximately 80-90% of those antibiotics are prescribed in an outpatient setting. Of concern, it is estimated that twenty-eight percent of all prescribed antibiotics are inappropriately prescribed in U.S. doctors’ offices and emergency departments (Clin Infect Dis. 2021;72(1):133-137).

 

Multiple microorganisms may cause infections and include bacteria, viruses, fungi, and parasites. Antibiotics are agents that either stop the growth (bacteriostatic) or produce bacterial death (bactericidal) of specific species of bacteria. The choice of selecting the right antibiotic for the patient is multifactorial. A patient with pneumonia acquired in the outpatient setting (community-acquired pneumonia) differs from a patient diagnosed with pneumonia in the hospital (hospital-acquired pneumonia). Healthcare providers utilize infectious disease evidence-based guideline recommendations for specific bacterial infections. The healthcare provider will order blood or urine (for urinary tract infections) cultures and sensitivities to help choose the most appropriate antibiotic for the patient. The initial choice of antibiotics will have a broad coverage of multiple bacterial organisms. Once the culture and sensitivity reports are received, the healthcare provider can narrow the antibiotic coverage based on the results. The culture and sensitivity report will have the bacteria species that grew on the petri dish and a list of antibiotic sensitivities to the bacteria. The goal is to give antibiotics that will kill the bacteria and not be resistant to the bacteria.

 

Bacterial resistance to antibiotics is an ongoing issue in the infectious disease arena. Some bacteria have evolved a natural resistance to antibiotics that are being prescribed. There is a phenomenon of acquired resistance where a bacterium develops resistance to the antibiotic after being exposed to an antibiotic. Bacteria have processes that break down the antibiotic, efflux pumps that eliminate the antibiotic, and enzymes that alter the antibiotic. Resistance may occur if a patient is administered an inappropriate antibiotic that does not kill the bacterial infection. Non-compliance with antibiotics for the duration of therapy by the patient can also cause bacterial resistance. Administering antibiotics to a patient with a viral infection may also cause bacterial resistance.

 

Allergies to antibiotics play a considerable role in which class of antibiotics can be given safely to a patient. An anaphylactic reaction may occur after administering an antibiotic. Anaphylaxis is a life-threatening condition that may be marked by dizziness or lightheadedness, difficulty breathing, swelling of the tongue or throat, seizures, shallow blood pressure, vomiting, diarrhea, and abdominal cramps. In my experience, a penicillin allergy is the most commonly reported drug allergy in clinical practice. If I see a penicillin allergy on a patients record, I need to know what symptoms the patient had when exposed to penicillin. If the patient says, I stopped breathing, and my throat closed (anaphylaxis), I must choose another antibiotic to cover the infectious bacteria. True penicillin allergies are reported in ten percent of the U.S. population; however, nine out of ten patients who report penicillin allergies are not truly allergic. Eighty percent of genuinely allergic patients will lose the penicillin allergy in ten years. There is a procedure where patients can be de-sensitized to penicillin. The penicillin-allergic patient receives a small dose of penicillin and is given progressively larger doses every 15 to 30 minutes over several hours or days. The intensive care unit carefully monitors the patient after each dose, and supportive care is available to treat allergic reactions.


How antibiotics affect t
he gut microbiome must be considered when a patient has completed an entire course of antibiotic therapy.
The human gut contains around 100 trillion bacteria, including five hundred different bacterial species, weighing approximately 2 kilograms (Nutr Rev. 2012;70(Suppl 1): S10–13). The human colon contains hundreds of species of bacteria, which collectively play an important role in digestion and health. A long course of antibiotics or several short courses of antibiotic therapy can disrupt the gut flora. The bacteria that play a role in gut health can be killed by antibiotics, which changes the population dynamic in the gut. A significant change in the gut is an overgrowth of other microorganisms kept in check by the bacteria eliminated by the antibiotic. The most crucial problem is the overgrowth of Clostridium difficile (C.diff). Clostridium difficile is an infection of the colon that causes more than three bouts of diarrhea per day and, in severe cases, ten to fifteen episodes of diarrhea daily. C. diff must also be treated with specific antibiotics. Patients over 65 years of age carry a higher risk of contracting Clostridium difficile if they have been on antibiotics for at least a week, have a weakened immune system, and have made recent visits to a hospital or skilled nursing facility. Some medical literature recommends administering either probiotics or prebiotics after antimicrobial therapy to strengthen gut health. 

As a former antimicrobial stewardship pharmacist, I have learned choosing the most appropriate antibiotic for each patient requires a dynamic thought and decision process. So, if you ever require antibiotics, remember to take the antibiotic as prescribed for the duration of the therapy. Most of the time, the patient will feel a little worse in the first couple of days and then begin to feel better. Do not stop the antibiotic prematurely. Let your healthcare provider know of any drug allergies to specific antibiotics. Remember also that antibiotics do not treat viral infections. And use good judgment with the IMSAFE acronym before flying after being treated with antibiotics. For myself, I wait seven to 10 days post-infection before hitting the airways. Be well and fly safe.

Larry M. Diamond, PharmD, CFII
Larry Diamond has a Doctor of Pharmacy Degree and has been a pharmacist for 37 years. Larry’s pharmacy practice has been as a Clinical Pharmacy Specialist in Cardiology, Orthopedic Surgery Specialist and most recently Clinical Pharmacy Coordinator. He is a CFII, a pilot for 33 years and has been an AOPA member since 1984.
Topics: Pilot Protection Services

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